HR+/HER2- Breast Cancer: Identifying Barriers to Use of CDK4/6 Inhibition


Comprehensive insight on the barriers to CDK4/6 inhibition in HR+/HER2- breast cancer, from both medical and accessibility perspectives.


Hope S. Rugo, MD, FASCO: Let us discuss the use of CDK4/6 inhibitors a little further; is there any patient where you wouldn’t use a CDK4/6 inhibitor, Mark? Have you found a patient?

Mark Pegram, MD: Maybe if they’re allergic to it, but I was so struck by the subset analysis in PALOMA-2 [NCT01740427] where they looked at all the variables: bone-only disease, age, even very advanced age, they looked at on the forest plot. They looked at some very long disease-free intervals and there was still a significant benefit by adding the CDK4/6 inhibitor in that data set; it’s just astonishing. You can’t really—based on clinical demographic or pathologic features—you can’t identify a subset of patients who doesn’t statistically benefit from the addition of CDK4/6. I don’t find any good reason not to use it. In this country, looking at some postmarketing research data, the penetration in the first line for use of CDK4/6 inhibitors is not 100%, it’s not even close. There’s a stubborn 20% or so right now that are getting chemotherapy first, which is not appropriate in as much as CDK4/6 inhibitors are arguably even more efficacious and less toxic; that probably has to do with cost. These drugs are very expensive, and the co-pays are very high, consequently there may be a subset of patients for whom it may be difficult to get the drug. Now, for patients who don’t have any resources, all the manufacturers for all 3 of these have very fine programs where you can get drug access, no problem. But it’s everyone in the middle who has a real job, a career, a family, is a retiree: those are the patients where it may be tough to make those co-pays. I suspect that’s why in market research data it hasn’t caught up to where we think it should be as academics.

Hope S. Rugo, MD, FASCO: Medicare share of cost, depending on the Part D plan that a patient has, can be quite daunting for some. Does anybody else have a different opinion on who you wouldn’t give a CDK4/6 inhibitor to?

Komal Jhaveri, MD, FACP: I think somebody who had a toxicity issue. Very rarely that can happen, despite multiple dose reductions they did not have tolerance and still have the neutropenia. They couldn’t take it, or diarrhea was an issue with abemaciclib and they just couldn’t take that on, especially in somebody who has a very endocrine-sensitive disease and an extremely long disease-free interval from their adjuvant therapy; maybe a few bone metastases only. A very elderly patient population potentially one could consider that as an option, as well. Short of that, I would agree that “Why not use a CDK4/6?” is a very appropriate question rather than thinking about why we should not give it to them.

Mark Pegram, MD: I think somebody mentioned previously that someone perhaps who’s very elderly with multiple medical comorbidities, competing causes of mortality, or the breast cancer is probably not going to be the problem in the end; certainly some of those patients could be treated well without a CDK4/6 inhibitor, but just about everybody else with a reasonable performance status, I think CDK4/6 inhibition is the best.

Hope S. Rugo, MD, FASCO: Except for if you get ILD [interstitial lung disease], which I currently have one patient; ILD on abemaciclib got better, ILD on ribociclib, OK, I give up. It’s the only patient I’ve ever seen with symptomatic ILD. It’s very rare.

Komal Jhaveri, MD, FACP: It is very rare. I think I have one patient in clinic as well that just had it, so it’s only one that I had.

Hope S. Rugo, MD, FASCO: We don’t know the risk factors for interstitial lung disease other than being from Japan and probably overall some subset of Asian descent, other than that, we don’t know. My patient was Russian, so didn’t fit into that group. The other decisions that we make about treatment, we talked about menopausal status; it’s not very common, but if a patient comes in with brain [metastases] or with hormone receptive positive diseases, does that change your decision about the CDK4/6 inhibitor partner?

Komal Jhaveri, MD, FACP: It does. The data that we have currently for the CDK4/6 inhibitors, it does appear that abemaciclib might be more active in the brain, so certainly that would be one scenario where I would favor abemaciclib over the other CDK4/6 inhibitors and choose that for that particular patient. I’ve done that in clinic for a few handfuls of patients who did present with brain metastases at the time of the diagnosis. That doesn’t happen very commonly in HR-positive disease, but in the handful of patients that it has, I have chosen abemaciclib as my first choice.

Hope S. Rugo, MD, FASCO: Anyone with similar thoughts?

Anne O’Dea, MD: I agree.

Transcript edited for clarity.

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